Establishment of pharmacogenetic-based dosing algorithm of warfarin for Asian, Caucasian and African American patients

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To establish the initiating dosing algorithm of warfarin in 3 different populations (Asian, African American and Caucasians), pharmacokinetic (PK) and pharmacodynamic (PD) factors associated with inter-individual variability in anti-coagulation responses were investigated by performing the retrospective and prospective clinical studies.Multivariate analyses showed that mutations of CYP2C9*8,CYP2C9*3,CYP2C9*2, sex and age were predictors of PK (clearance) and that mutations of VKORC1*2 & CYP4F2*3 and the baseline coagulation activity were predictors of PD (IC50 & the non-linear index). Furthermore, all results indicate that factors associated with the reduced metabolic activity of warfarin might be critical determinants of the over-anticoagulation response during initiation therapy in Asian patients.